ISSN:0885-3177    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:0885-3177    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Cystic fibrosis (CF) is a disease that affects the function of specialized epithelial cells within the lungs, gut, pancreas, sweat glands, and male genital ducts. Following the cloning of the CF gene, it is possible to examine tissue-specific expression of this gene. To investigate the onset of the CF disease process, expression of the CF gene in midtrimester human fetal tissues has been analyzed by in situ hybridization using antisense RNA probes. The major site of CF gene expression at this stage of development is in the pancreas. Within the pancreas, CF mRNA is seen to be largely restricted to the epithelium of intralobular and small interlobular ducts.

ISSN:0885-3177    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Glucocorticoids are effective in the treatment of certain leukemias and lymphomas, but their effects on the growth of several solid tumors have not been determined. We report here that cortivazol (CVZ), a potent synthetic glucocorticoid, inhibits the growth of a hamster pancreatic adenocarcinoma, H2T, in vivo. CVZ regulation of glucocorticoid receptor (GR) expression was followed as a specific molecular correlate. H2T cells were injected into cheek pouches of male Syrian golden hamsters, where they formed readily measurable tumors. Two studies were performed. In the first, hamsters were randomized to three groups immediately after injection of tumor cells: control, CVZ (0.1 μg/g body wt), or CVZ (0.3 μg/g body wt). Injections of either CVZ or its vehicle were administered on a 14-day cycle of 5 treatment days, followed by 9 days off treatment. Tumors were measured and areas calculated weekly. On day 48, the hamsters were killed and the tumors excised, weighed, and analyzed for DNA, RNA, and protein content. In the second study, randomization and treatment schedule were as before, except that on day 33 the hamsters were killed, tumors were excised and weighed, and total RNA from the tumors was isolated. GR mRNA content was determined by filter hybridization with a32P-labeled GR cDNA probe, and the signal normalized by reprobing for a-tubulin as an invariant, independent signal. At either dose, CVZ significantly inhibited H2T tumor area and weight and DNA, RNA, and protein content. Body weights of animals treated with CVZ were not significantly decreased as compared with controls. In addition, GR mRNA in H2T cells was increased approximately twofold by CVZ. These results suggest that the positive induction of GRs in H2T may correlate with the inhibition of tumor growth. CVZ deserves further examination as a useful adjuvant treatment for certain pancreatic cancers.

ISSN:0885-3177    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

In vivo fluorescent microscopy with direct observation of flow through the islet was used to investigate the islet microcirculation. In urethane-anesthetized rats (n = 18), the pancreas was exposed and an islet was identified under direct microscopy. The vertical illuminator for fluorescent microscopy was turned on and fluorescein-albumin conjugate or fluorescent microspheres were injected intravenously or intraarterially. Each study was videotaped; on slow motion playback, the flow of the conjugate or microspheres was followed through the islet, the islet capillaries, and then to venules exiting the islet. One islet in the head of the pancreas in 12 rats was studied. The arterioles first reached the surrounding mantle of the islet where they divided into capillaries that carried conjugate or microspheres to other portions of the mantle or the core of the islet. Flow of conjugate traversed the core and returned to different portions of the mantle. The fluorescent microsphere study permitted a more detailed study of the pathways followed, the individual microspheres being seen to travel through numerous tortuous pathways through the islet. The flow of microspheres was nonhomogeneous in that individual microspheres in one portion of the islet would stop, then move on, while other microspheres flowed freely. The capillaries joined two to six venules that carried the conjugate or microspheres out of the islet. One or two of the exiting microvessels entered the adjacent acinar microcirculation; the others entered larger collecting venules. In six tail islets studied, the microcirculation was similar to that of the islets in the head of the pancreas. The fluorescent in vivo microscopy technique permitted delineation of a complex pattern of flow through the islet microvasculature that suggests there is not a simple B- to A to D-cell order of cellular perfusion.

ISSN:0885-3177    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Changes of pancreatic blood flow (PBF) during acute pancreatitis (AP) have been under investigation by means of electromagnetic flowmeters, radioactive microspheres, isotope fractionation, radioactive gas clearance, and venous outflow techniques. All methods, however, have certain drawbacks, which make the application of other techniques desirable. In this study, the hydrogen clearance technique (HCT) was tested for the first time in a well established foxhound model of AP. PBF, systemic blood pressure, and heart rate were monitored over 90 min after the onset of AP and 60 min after therapeutic infusion of Dextran-40 (10 ml/kg body wt). Our results fully agree with the data found by other techniques in this experimental model. Sixty-five of 73 electrodes implanted into the pancreas of eight foxhounds were found working. From 1,024 registered clearance curves, 876 were identified as monoexponential. In the other cases, and only then, we found either dislocation of the electrode tips (n = 6) or perielectrodal hemorrhage during histological examination (n = 4). We believe that the HCT is a feasible and reliable tool for measuring PBF in experimental settings like AP.

ISSN:0885-3177    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

In this study, changes in the microcirculatory dynamics of the pancreas in response to normal feeding, sham feeding, and truncal vagotomy were investigated to elucidate the involvement of a neural mechanism in the physiological modulation of pancreatic blood flow in the conscious state. Continuous measurement of changes in the microcirculation of the pancreas was performed in conscious dogs by the thermoelectric method. A meat med was given to six normal dogs, seven dogs constructed with external esophagostomy (sham feeding), and four dogs with truncal vagotomy. In response to normal feeding, pancreatic blood flow attained the peak increase of 65.2 ± 6.276, showing a significant and biphasic response until ∼120 min. After sham feeding, pancreatic blood flow was significantly increased with peak values of 89.0 ± 19.0%, but thereafter showed a rapid decrease, returning to the basal level already at 7.2 ± 1.1 min. Although truncal vagotomy significantly and greatly reduced the peak increase of pancreatic blood flow to 28.2 ± 5.176, blood flow showed still a significant and sustained elevation above basal. This study provides evidence for the involvement of the neural mechanism in the physiological modulation of the microcirculation of the pancreas in the conscious state. The results strongly suggest that the cephalic phase of the increase in pancreatic blood flow is vagally mediated.

ISSN:0885-3177    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Insulin response to glucose is severely impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM). Also in a rat model of NIDDM, neonatally streptozotocin diabetic rats (STZ), the insulin response to glucose is profoundly suppressed when studied in vivo or in the perfused pancreas. The insulin response was better preserved from isolated islets obtained from patients and STZ rats. Since α2-adrenoceptor stimulation suppresses insulin secretion, catecholamines from intrapancreatic nerve terminals may be involved in the mechanism behind the marked impairment of the glucose-stimulated insulin response in the intact pancreas. We have studied the pancreatic content and release—or overflow—of catecholamines from the isolated, perfused pancreas of STZ rats. The overflow of noradrenaline (NA) in the perfusate was two- to threefold higher in pancreata from STZ than from nondiabetic rats, and perfusion with a high glucose concentration increased the NA overflow in both types of pancreata. Levels of adrenaline (ADR) were always low in perfusates of nondiabetic glands, but increased in five of seven perfusions of STZ glands. The pancreatic contents of NA and ADR were similar in STZ and nondiabetic rats. Pretreatment of rats with reserpine 24 h before perfusions reduced the pancreatic content of NA and ADR by >90% in both STZ and nondiabetic rats. Reserpine also diminished the overflow of NA in the perfusate from STZ rats by >90% and from nondiabetic rats by 58–77%. After reserpine, however, glucose-induced insulin release was not enhanced in either STZ or control pancreata. In conclusion, overflow of catecholamines is higher in the pancreas of STZ than of nondiabetic rats. It is unlikely, however, that these increased levels of pancreatic catecholamines are responsible for the severely impaired glucose-induced insulin release from the isolated, perfused STZ rat pancreas.

ISSN:0885-3177    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The role of gastric inhibitory polypeptide (GIP) on insulin secretion in the presence of different glucose concentrations has been studied in perifused microdissected murine islets. Insulin secretion was concentration dependent in the presence of glucose alone: Switching the perifusion buffer from 5.5 to 11.1 and 22.2 mMglucose caused an increase in insulin response assessed as the total integrated area under the curve over a 20-min period (6.4 ± 0.48 and 12.1 ± 0.58 ng, respectively; p <0.01, n = 6). If 11.1 mMglucose perifusion in the presence of GIP was preceded by 5.5 mMglucose alone, the integrated insulin secretionR0 min above basal level was attenuated (1.46 ± 0.10 vs. 0.37 ± 0.03 ng; p <0.01, n = 6), and withdrawal of GIP from the perifusion buffer resulted in the restoration of 11.1 mMglucose-stimulated insulin secretion (1.46 ± 0.10 vs. 1.98 ± 0.12 ng). If islets were continuously perifused with 11.1 mMglucose, the addition of GIP did not alter insulin secretion. In contrast, the addition of GIP to 22.2 mMglucose perifusion buffer further enhanced the high glucose-induced insulin secretion above basal (12.1 ± 0.58 vs. 14.5 ± 0.84 ng; p <0.05, n = 6). These observations are consistent with a hypothesis that during a low glucose condition, GIP prevents the risk of hypoglycemia by suppressing insulin secretion, while during a high glucose load, glucose-induced insulin stimulation is potentiated by GIP, presumably to prevent hyperglycemia.

ISSN:0885-3177    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The effects of glucose, tolbutamide, and diazoxide on K+permeability in neonatal and adult rat pancreatic islets, maintained in culture 1 week, were investigated by measuring the86Rb outflow rate from prelabeled islets. In the absence of glucose, the86Rb efflux was significantly lower in neonatal than adult islets. Raising the glucose concentration to 2.8, 5.6, 8.3, and 11.1 mMproduced a marked reduction in the86Rb efflux in adult islets but only a minor reduction in neonatal islets. The effect of tolbutamide to reduce, and diazoxide to increase, the86Rb efflux was also less in neonatal islets. These results are discussed with respect to previously reported differences in insulin secretion from neonatal and adult islets in culture.

ISSN:0885-3177    

出版商:OVID    

年代:1993

数据来源: OVID